ABSTRACT: B Cell Core?Core 2 Mother-to-child transmission (MTCT) remains a global health problem and results in many infant/child HIV-1 infections each year. Development of a vaccine that can reduce HIV-1 transmission due to breastfeeding would leverage the established benefits of breastfeeding in resource poor settings while decreasing infection rates. The purpose of this HIVRAD application is to determine if a vaccine strategy in infants, mothers, or both, could reduce MTCT due to breastfeeding. The studies proposed in this application will use a rhesus macaque model to determine the ability of a vaccine to reduce breastfeeding associated MTCT. This B Cell Core will quantify those responses that may correlate with infection risk to determine those responses critical for protection and to provide preliminary data for future human studies. Specifically, in Aim 1, we will quantify the functional activity, avidity, and recognized epitopes of antibodies elicited by maternal and infant vaccine regimens. In Aim 2, we will create a recombinant Env protein antigen-specific reagent to quantify the frequency and phenotype of vaccine-elicited Env-specific B cell responses in mothers and infants. This work will test the hypothesis that a higher frequency of vaccine-elicited antigen-specific B cells correlates with more potent ADCC, higher antibody avidity, binding of plasma antibodies to more epitopes, and greater protection following challenge. Finally, in Aim 3, we will define the B cell repertoire of Env-vaccinated infants in the setting of maternal vaccination. Using the same recombinant Env protein antigen-specific reagent made for Aim 2, we will sort infant antigen-specific B cells from infants for gene analysis and monoclonal antibody (mAb) production to test the hypothesis that placentally transferred maternal antibodies will recognize the same epitopes as the infant; such that mAbs from infants will have the same patterns of activity, avidity, and epitope specificity when compared with plasma antibody from mothers. The B Cell Core will provide critical data to the Program and significantly advance our understanding of B Cell responses required for protection against MTCT of HIV-1.